The overall objective of this proposed research remains the development and utilization of realistic mathematical network models of blood flow through microcirculatory system. These models should predict the local (as well as overall) flow parameters, such as the fluxes of plasma and cells (especially erythrocytes), and the responses of these variables to changes in such parameters as cell composition of the blood (hematocrit, white cell-red cell ratio, etc.), cell deformabilities and wall adhesivenesses, vessel parameters (diameters, lengths, cross sectional shapes, etc.) and pressures. These models would then be useful in predicting local concentrations and fluxes of oxygen and other substrates, metabolites, vasoactive agents, therapeutic drugs, etc. in microcirculatory vessels and adjacent tissue. They would also serve as a means of extending the usefulness of the limited amount of data which can be obtained in a single in vivo experiment, by providing a general framework through which the in vivo data can be more fully interpreted, as well as interpolated and extrapolated. This project will utilize altered blood cells from Projects 2 to determine the roles of cell deformability and volume in regulating blood flow through microvascular network, thereby permitting development of hemodynamic relationships which contain cell deformability and cell volume as independent parameters. Project 4 has been a major collaborator with this project, providing an opportunity to obtain in vivo microcirculatory data for testing hemodynamic relationships and computer simulation models; it has also provided us with an opportunity to test and improve currently used techniques for determining in vivo flow parameters. This collaboration will be expanded, and include computer simulation of in vivo flows studied in Project 4.